Proteoglycans are complex macromolecules which are found in abundance along with special collagens in the extracellular matrix of cartilage. Proteoglycans are composed of a variety of constituents which serve to structure water and function as a cushion at bone joints as well as imparting to cartilage a specialized function in developing embryos of forming a model which is replaced by bone. We have previously shown that chick limb mesenchymal cells in culture differentiate into chondrocytes and these cells synthesize cartilage proteoglycans. Proteoglycans are composed of specific regions which can be isolated and characterized. We have shown that the size and complexity of these regions change as cells in vitro progress from embryonic to mature and finally to senescent chondrocytes. We propose to provide a detailed chemical and physical characterization of the transitions of synthesis of proteoglycans during the embryonic and senescent periods. Several hypotheses have been put forth to account for those transitions. With the detailed chemical and physical characterizations of cartilage proteoglycans available, we propose to provide tests of these hypotheses. One of the possibilities is that the chick limb mesenchymal system will be a useful model for explaining aspects of osteoarthritis, especially if senescent chondrocytes synthesize a proteoglycan which does not effectively act to structure water and provide the appropriate cushioning properties of joint cartilage.